OVERVIEW

PRODUCT INFORMATION

CHEMICAL FORMULA AND STRUCTURE

View in own window

DRUG	CAS REGISTRY NUMBER	MOLECULAR FORMULA	STRUCTURE
Lomitapide	182431-12-5	C39-H37-F6-N3-O2

ANNOTATED BIBLIOGRAPHY

References updated: 20 May 2019

• Zimmerman HJ. Drugs used in the treatment of hypercholesterolemia and hyperlipidemia. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 660-2.

  (Expert review of hepatotoxicity published in 1999, before the availability of lomitapide).
• De Marzio DH, Navarro VJ. Hepatotoxicity of cardiovascular and antidiabetic medications. Lipid lowering agents. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 519-40.

  (Review of hepatotoxicity of lipid lowering agents; lomitapide is not discussed).
• Gurgle HE, Blumenthal DK. Drug therapy for dyslipidemias. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 605-18.

  (Textbook of pharmacology and therapeutics).
• Cuchel M, Bloedon LT, Szapary PO, Kolansky DM, Wolfe ML, Sarkis A, Millar JS, et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med 2007; 356: 148-56. [PubMed: 17215532]

  (Among 6 patients with familial hypercholesterolemia treated with 4 doses of lomitapide for 4 weeks, LDL cholesterol levels decreased by 51% and triglycerides by 65% at the highest dose and ALT elevations arose in 4 patients, all of whom also had increases in hepatic fat by MRI [10-40%]).
• Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, including 6 due to statins, but none to lomitapide).
• Two new drugs for homozygous familial hypercholesterolemia. Med Lett Drugs Ther 2013; 55 (1413): 25-7. [PubMed: 23545581]

  (Concise review of the mechanism of action, efficacy, safety and costs of lomitapide shortly after its approval for use in the US; mentions that it can cause elevations in aminotransferase levels and increases in hepatic steatosis for which reason it is only available through a restricted access program).
• Cuchel M, Meagher EA, du Toit Theron H, Blom DJ, Marais AD, Hegele RA, Averna MR, et al.; Phase 3 HoFH Lomitapide Study investigators. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet 2013; 381 (9860): 40-6. [PMC free article: PMC4587657] [PubMed: 23122768]

  (Among 28 patients with familial hypercholesterolemia treated with escalating doses of lomitapide [5 to 60 mg daily], LDL cholesterol decreased by 50%, but side effects were common, mostly gastrointestinal [>90%] and ALT elevations above 3 times ULN occurred in 10 [36%] and above 5 times ULN in 4 [14%], but none required drug discontinuation and none were associated with jaundice or symptoms, but were accompanied by increases in liver fat [from <2% to ~8%]).
• Raal FJ. Lomitapide for homozygous familial hypercholesterolaemia. Lancet 2013; 381 (9860): 7-8. [PubMed: 23122767]

  (Editorial on familial hypercholesterolemia in response to article by Cuchel et al. [2013]).
• Davis KA, Miyares MA. Lomitapide: A novel agent for the treatment of homozygous familial hypercholesterolemia. Am J Health Syst Pharm 2014; 71: 1001-8. [PubMed: 24865757]

  (Review of the mechanism of action, efficacy and side effects of lomitapide).
• Rader DJ, Kastelein JJ. Lomitapide and mipomersen: two first-in-class drugs for reducing low-density lipoprotein cholesterol in patients with homozygous familial hypercholesterolemia. Circulation 2014; 129: 1022-32. [PubMed: 24589695]

  (Summary of mechanism of action of microsomal triglyceride transport protein [MTTP] inhibitors, their efficacy, adverse event rates, clinical usefulness and need for further research).
• Sacks FM, Stanesa M, Hegele RA. Progression to hepatitis and fibrosis secondary to lomitapide use--reply. JAMA Intern Med 2014; 174: 1522-3. [PubMed: 25178869]

  (44 year old woman with severe hypertriglyceridemia and recurrent pancreatitis was treated with lomitapide for 13 years with excellent control of lipid levels, but with fluctuating ALT levels and development of steatohepatitis eventually with significant fibrosis).
• Miyares MA. Progression to hepatitis and fibrosis secondary to lomitapide use: selecting the next course of action. JAMA Intern Med 2014; 174: 1522. [PubMed: 25178868]

  (Letter in response to article by Sacks [2014] questioning the use of lomitapide for 13 years in the face of signs of steatohepatitis).
• Cuchel M, Blom DJ, Averna MR. Clinical experience of lomitapide therapy in patients with homozygous familial hypercholesterolaemia. Atheroscler Suppl 2014; 15: 33-45. [PubMed: 25257075]

  (Clinical review of efficacy and safety of lomitapide in 29 patients with familial hypercholesterolemia [Cuchel 2013] with in depth discussion of management of side effects including serum ALT elevations).
• Goulooze SC, Cohen AF, Rissmann R. Lomitapide. Br J Clin Pharmacol 2015; 80: 179-81. [PMC free article: PMC4541964] [PubMed: 25702706]

  (Brief review of the mechanism of action and clinical use of lomitapide).
• Roeters van Lennep J, Averna M, Alonso R. Treating homozygous familial hypercholesterolemia in a real-world setting: Experiences with lomitapide. J Clin Lipidol 2015; 9: 607-17. [PubMed: 26228681]

  (Details of 4 European patients with familial hypercholesterolemia treated in the "real-world" including one who developed recurrent serum ALT elevations [from 16 to 230 U/L and then from 48 to 132 U/L] and increased liver fat with modest doses of lomitapide [5-10 mg daily], ultimately requiring drug discontinuation).
• Raper A, Kolansky DM, Sachais BS, Meagher EA, Baer AL, Cuchel M. Long-term clinical results of microsomal triglyceride transfer protein inhibitor use in a patient with homozygous familial hypercholesterolemia. J Clin Lipidol 2015; 9: 107-12. [PMC free article: PMC4563802] [PubMed: 25670368]

  (49 year old woman with familial hypercholesterolemia and cardiac complications was treated with lomitapide [40-60 mg daily] and had intermittent ALT elevations [peak ~10 times ULN, but without jaundice or symptoms], but responded to discontinuation and abnormalities did not recur on restarting).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 41 cases [5.4%] were attributed to lipid-lowering agents, including 31 due to statins, 5 to niacin and 5 to fibrates, but none to lomitapide).
• Lomitapide (Lojuxta). Use only in homozygous familial hypercholesterolaemia, with caution. Prescrire Int 2015; 24: 176-8. [PubMed: 26240881]

  (Commentary on lomitapide stressing its potential for causing liver injury and need to limit its use to patients with homozygous familial hypercholesterolemia).
• Stefanutti C, Morozzi C, Di Giacomo S, Sovrano B, Mesce D, Grossi A. Management of homozygous familial hypercholesterolemia in real-world clinical practice: A report of 7 Italian patients treated in Rome with lomitapide and lipoprotein apheresis. J Clin Lipidol 2016; 10: 782-9. [PubMed: 27578108]

  (Description of 7 patients with familial hypercholesterolemia treated with lomitapide, all on lipoprotein apheresis, in whom careful titration of dose was associated with lower rates of gastrointestinal side effects and no patient had to stop therapy because of ALT elevations).
• Sanna C, Stéphenne X, Revencu N, Smets F, Sassolas A, Di Filippo M, Descamps OS, et al. Homozygous familial hypercholesterolemia in childhood: Genotype-phenotype description, established therapies and perspectives. Atherosclerosis 2016; 247: 97-104. [PubMed: 26894473]

  (Among 8 patients with familial hypercholesterolemia, all had LDL-cholesterol levels of 500 mg/dL and only modest improvements with use of statins and ezetimibe compared to marked improvements after liver transplantation).
• D'Erasmo L, Cefalù AB, Noto D, Giammanco A, Averna M, Pintus P, Medde P, et al. Efficacy of lomitapide in the treatment of familial homozygous hHypercholesterolemia: results of a real-world clinical experience in Italy. Adv Ther 2017; 34: 1200-10. [PubMed: 28432645]

  (Among 15 Italian patients with familial hypercholesterolemia treated with lomitapide, LCL-cholesterol levels fell in all from a mean of 493 to a nadir of 132 mg/dL, and no patient had ALT elevations above 5 times ULN or required discontinuation for liver test abnormalities).
• Chacra APM, Ferrari MC, Rocha VZ, Santos RD. Case report: The efficiency and safety of lomitapide in a homozygous familial hypercholesterolemic child. J Clin Lipidol 2019 Mar 11. pii: [Epub ahead of print] [PubMed: 30948303]

  (7.6 year old girl with familial hypercholesterolemia was treated with lomitapide and after 3.5 years LDL-cholesterol levels fell from 428 to 266 mg/dL and ALT and AST levels remained unchanged).
• Ben-Omran T, Masana L, Kolovou G, Ariceta G, Nóvoa FJ, Lund AM, Bogsrud MP, et al. Real-world outcomes with lomitapide use in paediatric patients with homozygous familial hypercholesterolaemia. Adv Ther 2019 May 17. [Epub ahead of print] [PMC free article: PMC6824397] [PubMed: 31102204]

  (Among 11 children at 10 centers in 8 countries treated with lomitapide, LDL-cholesterol levels fell from a mean of 419 to a nadir of 177 mg/dL, and 3 had ALT elevations but were managed with dose adjustment without stopping therapy).